%0 Journal Article %1 Friesen:2007:Cancer-Res:17332322 %A Friesen, C %A Glatting, G %A Koop, B %A Schwarz, K %A Morgenstern, A %A Apostolidis, C %A Debatin, K M %A Reske, S N %D 2007 %J Cancer Res %K cancer-research claudia_friesen dolophine fulltext methadone %N 5 %P 1950-1958 %R 10.1158/0008-5472.CAN-06-3569 %T Breaking chemoresistance and radioresistance with 213Bianti-CD45 antibodies in leukemia cells %U https://www.ncbi.nlm.nih.gov/pubmed/17332322 %V 67 %X Chemoresistance and radioresistance are considered one of the primary reasons for therapeutic failure in leukemias and solid tumors. Targeted radiotherapy using monoclonal antibodies radiolabeled with alpha-particles is a promising treatment approach for high-risk leukemia. We found that targeted radiotherapy using monoclonal CD45 antibodies radiolabeled with the alpha-emitter (213)Bi ((213)Bianti-CD45) induces apoptosis, activates apoptosis pathways, and breaks beta-irradiation-, gamma-irradiation-, doxorubicin-, and apoptosis-resistance in leukemia cells. In contrast to beta-irradiation-, gamma-irradiation-, and doxorubicin-mediated apoptosis and DNA damage, (213)Bianti-CD45-induced DNA damage was not repaired, and apoptosis was not inhibited by the nonhomologous end-joining DNA repair mechanism. Depending on the activation of caspase-3, caspase-8, and caspase-9, (213)Bianti-CD45 activated apoptosis pathways in leukemia cells through the mitochondrial pathway but independent of CD95 receptor/CD95 ligand interaction. Furthermore, (213)Bianti-CD45 reversed deficient activation of caspase-3, caspase-8, and caspase-9, deficient cleavage of poly(ADP-ribose) polymerase, and deficient activation of mitochondria in chemoresistant and in radioresistant and apoptosis-resistant leukemia cells. These findings show that (213)Bianti-CD45 is a promising therapeutic agent to break chemoresistance and radioresistance by overcoming DNA repair mechanisms in leukemia cells and provide the foundation for discovery of novel anticancer compounds.

@article{Friesen:2007:Cancer-Res:17332322, abstract = {Chemoresistance and radioresistance are considered one of the primary reasons for therapeutic failure in leukemias and solid tumors. Targeted radiotherapy using monoclonal antibodies radiolabeled with alpha-particles is a promising treatment approach for high-risk leukemia. We found that targeted radiotherapy using monoclonal CD45 antibodies radiolabeled with the alpha-emitter (213)Bi ([(213)Bi]anti-CD45) induces apoptosis, activates apoptosis pathways, and breaks beta-irradiation-, gamma-irradiation-, doxorubicin-, and apoptosis-resistance in leukemia cells. In contrast to beta-irradiation-, gamma-irradiation-, and doxorubicin-mediated apoptosis and DNA damage, [(213)Bi]anti-CD45-induced DNA damage was not repaired, and apoptosis was not inhibited by the nonhomologous end-joining DNA repair mechanism. Depending on the activation of caspase-3, caspase-8, and caspase-9, [(213)Bi]anti-CD45 activated apoptosis pathways in leukemia cells through the mitochondrial pathway but independent of CD95 receptor/CD95 ligand interaction. Furthermore, [(213)Bi]anti-CD45 reversed deficient activation of caspase-3, caspase-8, and caspase-9, deficient cleavage of poly(ADP-ribose) polymerase, and deficient activation of mitochondria in chemoresistant and in radioresistant and apoptosis-resistant leukemia cells. These findings show that [(213)Bi]anti-CD45 is a promising therapeutic agent to break chemoresistance and radioresistance by overcoming DNA repair mechanisms in leukemia cells and provide the foundation for discovery of novel anticancer compounds.}, added-at = {2017-06-21T20:44:08.000+0200}, author = {Friesen, C and Glatting, G and Koop, B and Schwarz, K and Morgenstern, A and Apostolidis, C and Debatin, K M and Reske, S N}, biburl = {https://www.bibsonomy.org/bibtex/227ca84ed8da2cf827b461436f7d988c2/marcsaric}, description = {Breaking chemoresistance and radioresistance with [213Bi]anti-CD45 antibodies in leukemia cells. - PubMed - NCBI}, doi = {10.1158/0008-5472.CAN-06-3569}, interhash = {71351f4014618f1cadf01d9fdfea4325}, intrahash = {27ca84ed8da2cf827b461436f7d988c2}, journal = {Cancer Res}, keywords = {cancer-research claudia_friesen dolophine fulltext methadone}, month = mar, number = 5, pages = {1950-1958}, pmid = {17332322}, timestamp = {2017-06-21T20:44:08.000+0200}, title = {Breaking chemoresistance and radioresistance with [213Bi]anti-CD45 antibodies in leukemia cells}, url = {https://www.ncbi.nlm.nih.gov/pubmed/17332322}, volume = 67, year = 2007 }